Patent Grant
10777401
This application is a National Stage Application of PCT Application No. PCT/IB2016/057626, filed Dec. 14, 2016, which claims priority to DE Patent Application No. 10 2015 122 155.1, filed Dec. 17, 2015. The disclosures of each of these documents is hereby incorporated by reference in its entirety.
The invention relates to the technical field of ionizing a gaseous substance, in particular the ionizing or ionization of a gaseous substance in preparation for its analysis.
WO 2009/102766 describes a plasma probe ionizing a discharge gas through a dielectric barrier discharge. For ionizing a sample substance, the plasma probe is directed at a sample substance so as to ionize the sample substance. The ionized sample substance can be analyzed in a mass analysis unit arranged close to the sample substance. This kind of ionization leads to a repulsion of charged particles and to collisions with gas molecules, whereby a discharge can take place. This leads to a substantial loss of ions before the analysis and thus to a reduced sensitivity.
US 2013/0161507 A1 l discloses a mass spectrometer using, for the purpose of ionizing an analyte, the technique of dielectric barrier discharge. The published application especially aims at accomplishing a low voltage for discharge between two electrodes (cf. page 1, [0009]). To this end, a sample 101 to be analyzed has to be placed in a sample vessel 106 and enters due to a pressure gradient under vacuum a discharge area 114, where the ionization takes place. In the discharge area a pressure between 2 Torr and 300 Torr (between 266 Pa and 39900 Pa) prevails, the distance between the electrodes 112, 113 being between 1 mm and 100 mm (cf. page 2, [0035]). The vacuum in the discharge area 114 is necessary for achieving a low discharge voltage. In addition, a light illumination unit 116 is used, which irradiates an area and generates a discharge. Such a device (under vacuum) has a complex structural design and the necessity of placing a sample into the sample vessel allows an application only in the case of certain analyses.
It is the object of the present invention to provide a device, which is adapted to be used for ionizing a discharge gas and a sample substance in a flow-through mode without essentially destroying (fragmenting) the sample substance, which is usable under ambient conditions so as to avoid a high expenditure in terms of construction and equipment, and which ensures a high sensitivity in a possible analysis of an ionized substance.
This object is achieved by the use of an ionizing device, an ionizing device, which is adapted for use in an ionizing method and for the purpose of flow-through ionization. An analysis unit makes an ionized sample substance analyzable in an analyzer according to an analysis method.
The ionizing device or ionization device comprises at least two electrodes separated by a dielectric element. The dielectric element has the shape of a hollow body, so that a discharge gas and a sample substance can flow through the element. Outside the dielectric element a first electrode is arranged. The first electrode may be configured as a ring or as a hollow cylinder and may be pushed over the dielectric element or applied thereto. The second electrode is arranged inside the dielectric element. When a sufficiently high AC voltage is applied to one or both of the electrodes, a dielectric barrier discharge will be caused in a dielectric discharge region of the ionizing device. The ionization of gaseous substances takes place in and/or after the dielectric discharge region.
Surprisingly enough, it turned out that the ionizing efficiency or ionization efficiency depends to a considerable extent on the arrangement of the electrodes relative to one another, whereby, through an advantageous arrangement, the sensitivity of a possible subsequent analysis can be increased substantially. For a high ionization efficiency, the distance between the associated ends of the electrodes is between −5 mm and 5 mm (a detailed representation of the distance is is shown in
It will also be advantageous when the electrodes are spaced apart at a small distance perpendicularly to the direction of flow, but, taking into account the influence on the dielectric discharge that can take place between at least two electrodes, this distance may be configured in different ways.
Equally surprising is a highly efficient ionization of gaseous substances at a pressure of more than 40 kPa in the discharge area. The vacuum can be provided by a vacuum unit arranged at the outlet of the ionizing device.
The success desired and achieved by the present invention is the flow-through ionization of a sample substance for analysis. A so-called “soft” ionization is here used, which for the most part does not destroy or fragment the molecules, but leads to quasi-molecular ions through protonation and charge-transfer reactions. Especially in connection with (high-resolution) mass spectrometry, the substance can here be identified directly via its element composition. Due to the way in which the ionizing device and the ionizing method according to the present invention are configured, a very high sensitivity in the low femtogram to attogram range is achieved during a subsequent analysis.
The invention provides a highly efficient ionizing device (and a method associated therewith), which, in combination with mass spectrometry or ion mobility spectrometry, provides a highly sensitive “electronic nose” (in an analysis method) allowing a direct chemical analysis of molecules in the gaseous phase. Application possibilities are, in addition to classical combinations with chromatographic methods (GC, HPLC, Nano-LC), also direct screening analyses, e.g. a direct pesticide analysis on fruit or vegetable surfaces. For military or civil defense purposes, the technology may be used to detect toxic compounds or warfare agents. Especially in the case of chemical warfare agents, a very high sensitivity is required, since even the smallest concentrations of these agents may lead to poisoning that is dangerous to life. Another related field of application is forensics or security checks (narcotic or explosive wipe tests). Also a combination with sample preconcentration systems such as SPME is possible. The method can be used for medical “point of care” diagnostics (e.g. biomarker analysis in breath or in combination with SPME for hazardous and prohibited substances in blood, urine etc.).
The possibility of flow-through ionization simplifies sampling during analysis in general (“sucking in” analogously to the human nose), and this is important for rapid analysis applications or screening analyses, e.g. in industrial process control. Furthermore, the hitherto existing problem of an effective transfer of charged particles at atmospheric pressure into a vacuum (analysis) is solved. Due to the mutual repulsion of the charged particles, large parts of the ions formed are lost without being used in currently used processes for atmospheric is pressure ionization (e.g. ESI, HEST, APCI, DART, DESI, LTP). The formation of ions directly in or at the inlet guarantees an effective transfer of the charged particles for analysis and thus a high sensitivity.
Chemical analyses usually have to be carried out not only qualitatively but also quantitatively. Due to the problem of an “open” connection between the ionization and the analyzer, as with existing methods, the quantification can easily be interfered with by external influences (drafts, diffusion of impurities, etc.). This entails the problem of wrong or incorrect analysis results. Through a flow-through ionization, the connection between ionization and analyzer is closed and the above-described problem arising with respect to quantification is solved in this way.
Existing plasma-based ionization processes at quasi atmospheric pressure do not allow the analyte to be introduced into the discharge gas, since the analyte is destroyed in the discharge. This problem is solved by the formation of an extremely “soft” plasma with little or no fragmentation.
Just like the efficiency, the degree of fragmentation occurring depends partly on the composition of the surrounding atmosphere (humidity, etc.). Thus, a suitable selection of additive compounds (dopants) or gas compositions will allow to reduce or increase the ionization efficiency and/or fragmentation. The latter is particularly useful for portable applications, since portable systems themselves are usually not able to generate characteristic fragments that are used to identify the substances.
Furthermore, the invention allows a miniaturization of analysis devices and can be combined with portable systems, whereby the sensitivity of the latter is substantially increased. In addition, operation with batteries or rechargeable batteries is possible. No operating materials (except electrical energy) are required and analyses can be carried out in less than 100 ms. Furthermore, due to the miniaturizability and the structural design of the present invention, the invention can be combined with other, already existing ionization methods (e.g. ESI, APCI, etc.), thus allowing simultaneous detection of different analytes, such as the parallel ionization of very polar and non-polar substances.
A further development of the ionizing device comprises the introduction of so-called “dopant” substances (e.g. in chemical ionization) upstream or downstream of the ionizing device, for the purpose of increasing the selectivity or the sensitivity.
The ionizing device allows carrying out an efficient ionization in the dielectric barrier discharge region even at a pressure higher than 60 kPa, preferably higher than 80 kPa and particularly preferred at an essentially atmospheric pressure.
The distance between the associated ends of the first and second electrodes lies preferably between −3 mm and 3 mm, more preferably between −1 mm and 1 mm, particularly preferred is between −0.2 mm and 0.2 mm, and most preferably between −0.05 mm and 0.05 mm for a particularly high efficiency of ionization through a dielectric barrier discharge.
The second electrode, which is, at least sectionwise, arranged inside the dielectric element, may have the shape of a hollow cylinder or may be configured as a hollow body having a non-circular base area. Suitable basic shapes of a hollow body additionally comprise a triangular, a rectangular or an oval basic shape. The second electrode may also be configured as a wire that is arranged concentrically or eccentrically to the dielectric element. A small distance between the second electrode perpendicular to the direction of flow of the gaseous substances and the dielectric element will be advantageous. In particular, the distance is smaller than 0.5 mm and preferably smaller than 0.1 mm. Particularly good ionization results are achieved, when the second electrode is in contact with the inner side of the dielectric element.
The first electrode may be spaced apart from the dielectric element perpendicularly to the flow direction of the gaseous substances, the distance being preferably smaller than 5 mm. In particular, the second electrode is in contact with the outer side of the dielectric element. The best ionization results will be achieved when the first electrode is applied as a layer to the outer side of the dielectric element. In this way, parasitic discharges of the first electrode, which may also occur in the case of a (very) small distance (e.g. gas inclusions) between the first electrode and the dielectric element, can be avoided. The first electrode can be applied as a layer through a drying or curing liquid or suspension, e.g. a metal paint. The layer may also be applied to the outer side of the dielectric element through a transition from a gaseous phase into the solid phase. To this end, e.g. sputtering, CVD or PVD, or other coating techniques may be used.
The first and second electrodes are made of a conductive material (for electric current). In particular, they are made of a metal that is preferably silver or gold, contains a certain amount of silver or gold (also in the form of a layer) or consists of a metal alloy.
The dielectric element may consist of a plastic material (e.g. PMMA or PP) or preferably of quartz glass or of some other dielectric material.
The ionizing device has an inlet and an outlet. Through the inlet, a discharge gas and a sample substance can enter the ionizing device, where they can be ionized, at least partially, inside the device and from where they can exit the device through the outlet in an at least partially ionized condition. The area of the inlet through which the discharge gas and sample substance can flow is preferably larger than the flow-through area of the outlet. In particular, a flow limitation unit is arranged at the outlet of the device.
A flow through the ionizing device is preferably caused by a pressure gradient. Preferably, the pressure is higher at the inlet of the device than at the outlet of the device. Especially, the pressure prevailing at the outlet of the device is lower than atmospheric pressure while the is pressure prevailing outside the inlet is atmospheric pressure.
By arranging an analysis unit on the ionizing device, an analyzer can be established. Preferably, the ionizing device is directly connected to the analysis unit (optionally via a short intermediate element). The analysis unit is preferably a unit that is capable of carrying out an analysis on the basis of a molecular charge, e.g. a mass spectrometer, an ion mobility spectrometer or similar devices.
Preferably, the analyzer may have arranged therein, in addition to an ionizing device according to the present invention, at least one further ionizing device, e.g. a device for performing electron impact ionization, electrospray ionization or the like.
For an analyzer having a particularly simple structural design, the inlet of the ionizing device is open to the surroundings and the discharge gas is the atmosphere surrounding the inlet, in particular air. Other discharge gases may be used as well, such as nitrogen, oxygen, methane, carbon dioxide, carbon monoxide, at least one noble gas or mixtures thereof.
According to preferred embodiments, the ionizing device or the analyzer may be miniaturized such that a portability is given (e.g. handheld devices).
The ionizing device may be used in a method by means of which a discharge gas and a sample substance are ionized, especially in a flow-through mode. First, the discharge gas and the sample substance are introduced into the ionizing device through the inlet of the ionizing device, whereupon a voltage is applied between the first and second electrodes such that a dielectric barrier discharge will be caused in a dielectric barrier discharge region, and the discharge gas and/or the sample substance will be ionized in and/or after the discharge region.
For generating the dielectric barrier discharge, a voltage of up to 20 kV may be used, preferably a maximum of 10 kV and especially a maximum of 5 kV. Particularly good ionization results are achieved with a voltage between 1 kV and 3 kV.
The dielectric barrier discharge may be caused by unipolar voltage pulses (or high-voltage pulses) in order to minimize the effects of a displacement current and suppress thus e.g. undesired fragmentation reactions. The pulses preferably have a duration of 1 μs and in particular a maximum duration of 500 ns. The best results are achieved with pulses having a duration between 100 ns and 350 ns. The impulses or pulses have here preferably a frequency that is not higher than 1 MHz, in particular not higher than 100 kHz, and particularly preferred not higher than 25 kHz. The most energy-efficient ionization results are achieved at a frequency between 1 kHz and 15 kHz.
The voltage between the first and second electrodes may be applied by a sine-wave voltage, the sine-wave voltage of one of the first and second electrodes being preferably shifted by half a period relative to that of the other one of the first and second electrodes.
An analyzer may be used in a method according to which a discharge gas and a sample substance are introduced in the inlet of an ionizing device. A voltage is applied to the first and/or second electrode such that a dielectric barrier discharge will be caused in a dielectric barrier discharge region. In and/or after the dielectric barrier discharge region, the sample substance and/or the discharge gas are ionized, at least partially, and subsequently analyzed.
A voltage of up to 20 kV, preferably not higher than 10 kV, and especially not higher than 5 kV, can be used in the analysis method. Particularly good ionization results are achieved at a voltage between 1 kV and 3 kV.
The dielectric barrier discharge in the analysis method may be caused by unipolar voltage pulses (or high-voltage pulses) in order to minimize the effects of a displacement current. The pulses preferably have a duration of 1 μs and in particular a maximum duration of 500 ns. The best results are achieved with pulses having a duration between 100 ns and 350 ns.
The impulses or pulses preferably have a frequency that is not higher than 1 MHz, in particular not higher than 100 kHz, and particularly preferred not higher than 25 kHz. The most energy-efficient ionization results are achieved at a frequency between 1 kHz and 15 kHz.
The voltage between the first and second electrodes may be applied by a sine-wave voltage, the sine-wave voltage of one of the first and second electrodes being preferably shifted by half a period relative to that of the other one of the first and second electrodes.
An ionizing device can be used for flow-through ionization of a discharge gas and a sample substance. A discharge gas, such as air or some other atmosphere surrounding the inlet of the ionizing device, can be introduced continuously into the device. A sample can be introduced into the device discontinuously or continuously together with the discharge gas. Ionization takes place inside the ionizing device in a flow-through mode. When an analysis unit is connected to the ionizing device, it can in particular be ensured that the ionized sample substance to be analyzed will enter the analysis unit without interacting with discharge gas that has not passed through the ionizing device, as would be the case e.g. with plasma jets.
According to a further embodiment, an ionizing device may have a sample inlet that is arranged (downstream) of the discharge area. The sample inlet may, for example, be configured as a T-piece.
In the case of such an embodiment, a discharge gas may be introduced through an inlet of an ionizing device, viz. the ionizing device as described above or in the following, and ionized in the discharge area. In the discharge area, a dopant may be present in addition to the discharge gas. The dopant may, like the discharge gas, be introduced via the inlet of the ionizing device, or it may be introduced in the ionizing device via an additional inlet (dopant inlet). Thus, the discharge gas and/or the dopant is/are ionized in the ionizing device. The sample introduced after (downstream) of the discharge area reacts, especially through a charge transfer reaction, with the ionized discharge gas and/or dopant, whereby the sample will be ionized. Preferably, an absolute pressure of more than 40 kPa prevails in the ionizing device during ionization.
An ionizing device of the type described above or in the following may be used in such a way that a discharge gas and/or dopant is/are present during ionization in the discharge area, the discharge gas and/or the dopant being thus ionized. Preferably, an absolute pressure higher than 40 kPa prevails during ionization in the ionizing device. The ionized discharge gas and/or the dopant can leave the ionizing device in an ionized condition and meet a sample outside the ionizing device, whereby a reaction, in particular a charge transfer reaction, will take place between the ionized discharge gas and/or the dopant and the sample. Thus, a sample can be ionized.
According to a further embodiment, an ion mass filter may be connected to an ionizing device of the type described above or in the following. Through an ion mass filter a specific ion or specific ions is/are isolated or selected based on their mass or their mass-to-charge ratio. An example of an ion mass filter is a quadrupole. The ion mass filter may be arranged between the discharge area of an ionizing device and the sample inlet of the ionizing device, provided that the ionizing device has a sample inlet.
The ion mass filter may also be arranged between the discharge area of an ionizing device and the exit or outlet of the ionizing device. By using an ion mass filter, special ions of the discharge gas and/or of the dopant can be selected, which are brought into contact with a sample, whereby an improvement of the selectivity and/or sensitivity can be accomplished during an analysis of the ionized sample.
The ionizing devices described may be used in the analyzers, methods of ionizing or methods of analyzing described above or in the following.
The embodiments of the present invention are illustrated by means of examples and not in a manner in which restrictions from the figures are transferred to or read into the claims.
At the outlet A of the ionizing device 100, a vacuum unit 10 is arranged, in which a pressure below atmospheric pressure prevails, whereby a flow is caused in the ionizing device 100 and the pressure in the ionizing device 100 is controlled (by controlling the pressure in the vacuum unit 10). A vacuum unit 10 may be arranged on all embodiments of the ionizing device 100.
When a voltage, especially an AC voltage, is applied to one or both of the electrodes 1, 3, a dielectric barrier discharge can occur in a dielectric barrier discharge region 110 so as to ionize a discharge gas G or the sample substance S. The dielectric barrier discharge range 110 is only schematically shown in
According to another embodiment, the first and/or second electrode(s) 1, 3 may be positioned in the dielectric element 2 in such a way that the electrodes 1, 3 are insulated from each other.
The distance D between the associated ends of the electrodes 1, 3 can be seen best in
In
In
An arrangement of electrodes 1, 3 as in
The outlet A of an ionizing device 100 has arranged thereon a flow limitation unit 20 in
Flow regulation by means of a reduction of the cross-sectional area can be effected not only by a flow limitation unit 20 but also by other measures taken with respect to the structural design or control technology (e.g. through a controllable change in cross-section by means of a valve or through a variable vacuum). For example, a narrowing of the outlet A of the ionizing device 100 by means of a non-constant cross-section of the dielectric element 2 may be advantageous. Other suitable measures for regulating the pressure in the ionizing device 100 and/or the flow through the ionizing device may, however, be taken.
In
In
In addition to the embodiment shown in
An embodiment of the ionizing device 100 in
The first electrode 1, the dielectric element 2 and the second electrode 3 of the embodiment of the ionizing device 100 shown in
In other embodiments, various polygonal, elliptical and other basic shapes may be advantageous.
All the cross-sections of
An analyzer 200 shown in
| Number | Date | Country | Kind |
|---|---|---|---|
| 10 2015 122 155 | Dec 2015 | DE | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IB2016/057626 | 12/14/2016 | WO | 00 |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2017/103819 | 6/22/2017 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 4501965 | Douglas | Feb 1985 | A |
| 4948962 | Mitsui et al. | Aug 1990 | A |
| 5252827 | Koga et al. | Oct 1993 | A |
| 5961772 | Selwyn | Oct 1999 | A |
| 6320388 | Sun | Nov 2001 | B1 |
| 6407382 | Spangler | Jun 2002 | B1 |
| 6410914 | Park et al. | Jun 2002 | B1 |
| 6646256 | Gourley et al. | Nov 2003 | B2 |
| 7005635 | Ahern et al. | Feb 2006 | B2 |
| 7095019 | Sheehan et al. | Aug 2006 | B1 |
| 7119330 | Kalinitchenko | Oct 2006 | B2 |
| 7256396 | Reilly | Aug 2007 | B2 |
| 7667197 | Lin | Feb 2010 | B2 |
| 7807964 | Li | Oct 2010 | B2 |
| 7910896 | Marta et al. | Mar 2011 | B2 |
| 8247784 | Neidholdt et al. | Aug 2012 | B2 |
| 8368013 | Ishimaru | Feb 2013 | B2 |
| 8696996 | Albrecht | Apr 2014 | B2 |
| 8772710 | Ouyang et al. | Jul 2014 | B2 |
| 8803084 | Nishimura | Aug 2014 | B2 |
| 20030070913 | Miller et al. | Apr 2003 | A1 |
| 20070007448 | Wang | Jan 2007 | A1 |
| 20070114389 | Karpetsky et al. | May 2007 | A1 |
| 20080048107 | McEwen | Feb 2008 | A1 |
| 20100032559 | Lopez-Avila et al. | Feb 2010 | A1 |
| 20100301199 | Chen et al. | Dec 2010 | A1 |
| 20110108726 | Hiraoka et al. | May 2011 | A1 |
| 20110168881 | Sturgeon et al. | Jul 2011 | A1 |
| 20110253889 | Ishimaru | Oct 2011 | A1 |
| 20120292501 | Sugiyama | May 2012 | A1 |
| 20120292526 | Hiraoka et al. | Nov 2012 | A1 |
| 20140011282 | Ouyang et al. | Jan 2014 | A1 |
| 20140331861 | Makarov et al. | Nov 2014 | A1 |
| 20150069254 | Fernandez et al. | Mar 2015 | A1 |
| Number | Date | Country |
|---|---|---|
| 103177928 | Jun 2013 | CN |
| 104064429 | Sep 2014 | CN |
| 2450942 | May 2012 | EP |
| 2009102766 | Aug 2009 | WO |
| 2015077879 | Jun 2015 | WO |
| Entry |
|---|
| Kogelschatz; et. al Dielectric-Barrier Discharges. Principle and Applications. Journal de Physique IV Colloque, 1997, 07 (C4), pp. C4-47-C4-66 (Year: 1997). |
| PCT International Search Report, International Application No. PCT/IB2016/057626, dated Mar. 15, 2017, pp. 1-2. |
| S. Liu et al., Excitation of dielectric barrier discharges by unipolar submicrosecond square pulses, J. Phys. D: Appl. Phys. 34 (2001) 1632-1638. |
| M. M. Nudnova et al., Active capillary plasma source for ambient mass spectrometry; Rapid Commun. Mass Spectrom. 26 (2012) 1447-1452. |
| Z. Wu et. al., An Atmospheric Press Dielectric-barrier Discharge and ist Application for Detection of Environmental Pollutants, Advances in Biomedical Engineering 6 (2012) 133-139. |
| M. Sugiyama et al., Sensitive low-pressure dielectric barrier discharge ion source; Rapid Commun. Mass Spectrom. 27 (2013) 1005-1010. |
| L. Bregy et al., Real-time breath analysis with active capillary plasma inonization-ambient mass spectrometry, J. Breath Res. 8 (2014) 1-8. |
| J.-C. Wolf et al., Direct gas-phase detection of nerve and blister warfare agents utilizing active capillary plasma ionization mass spectrometry, Eur. J. Mass Spectrom. 21 (2015) 1-8. |
| J.-C. Wolf et al., Direct Quantification of Chemical Warfare Agents and Related Compounds at Low ppt Levels: Comparing Active Capillary Dielectric Barrier Discharge Plasma Ionization and Secondary Electrospray Ionization Mass Spectrometry, Anal. Chem. 87 (2015) 723-729. |
| Number | Date | Country | |
|---|---|---|---|
| 20180366310 A1 | Dec 2018 | US |
